title: Drugs associated with teratogenic mechanisms. Part I: dispensing rates among pregnant women in the Netherlands, 1998-2009.
abstract: OBJECTIVE
  What are the dispensing rates of drugs suspected to be associated with teratogenic mechanisms among pregnant Dutch women?
  
  
  CONCLUSIONS
  In a substantial proportion of pregnancies in our study population at least one drug associated with a teratogenic mechanism was dispensed in the first trimester of pregnancy.
  
  
  BACKGROUND
  The main teratogenic mechanisms of medical drugs that may affect fetal development in the first trimester of pregnancy have been described previously. However, information on the dispensing rate of such drugs among women at all stages of pregnancy is lacking.
  
  
  METHODS
  To determine how often medications suspected to be associated with a teratogenic mechanism are used by pregnant women, we studied 32 016 pregnancies included in the IADB.nl database between 1998 and 2009.
  
  
  METHODS
  We estimated dispensing rates of medical drugs suspected to be associated with teratogenic mechanisms in our study population. The IADB.nl database includes all pharmacy dispensings for an estimated population of 220 000 in 1994-1998 and c.500 000 since 1999. In addition, trends in first trimester dispensing rates over time and patterns of receiving multiple drugs associated with teratogenic mechanisms were evaluated. In addition, we determined the number of pregnancies in which multiple prescription drugs from one or more teratogenic categories were dispensed in the first trimester, and we evaluated the numbers of different medications dispensed that could be grouped within a specific teratogenic mechanism.
  
  
  RESULTS
  In 175 per 1000 pregnancies [95% confidence interval (CI), 171-179] at least one drug associated with a teratogenic mechanism was dispensed in the first trimester. The total dispensing rate was 236 per 1000 pregnancies (95% CI 232-241) in the 3 months before pregnancy and an increasing trend was seen in the second [214 per 1000 (95% CI 209-218)] and third [327 per 1000 (95% CI 322-332)] trimesters. The first trimester dispensing rates increased between 1998 and 2009 for selective serotonin-reuptake inhibitors (P < 0.001) and serotonin receptor agonists/antagonists (P < 0.001). In 71.8% of pregnancies in which drugs associated with teratogenic mechanisms were dispensed in the first trimester, women received drugs related to only one mechanism. Of the pregnancies in which drugs from multiple teratogenic categories were dispensed in the first trimester, 1148 (72.6%) women received drugs from 2 categories, 317 (20.0%) from three categories, 88 (5.6%) from 4 categories, 28 (1.8%) from 5 categories and 1 from 6 categories. Several women received multiple prescription medications grouped within a single teratogenic mechanism in the first trimester, ranging between 13.3% for cyclo-oxygenase inhibitors and 41.8% for serotonin receptor agonists/antagonists.
  
  
  CONCLUSIONS
  We used a dispensing database, therefore actual use of the medication prescribed is unknown and non-compliance could have led to overestimation of exposure prevalences.
  
  
  CONCLUSIONS
  Owing to the uncertainties concerning the safety of medication use during pregnancy, the results of this study stress the need for cautious prescription of medication associated with teratogenic mechanisms to women of reproductive age. This is further supported by our finding that women received multiple prescription medications grouped within a single teratogenic mechanism in the first trimester, which would theoretically increase strongly the risk of birth defects.
  
  
  BACKGROUND
  Marleen van Gelder was supported by the Netherlands Organisation for Scientific Research/NWO (grant no. 021.001.008). No competing interests are declared.
  
  
  BACKGROUND
  N/A.
authors.affiliation: Department for Health Evidence, Radboud University Nijmegen Medical Centre, Nijmegen 6500 HB, The Netherlands.
authors.forename: Marleen M H J
authors.initials: MM
authors.lastname: van Gelder
authors.forename: Jens H J
authors.initials: JH
authors.lastname: Bos
authors.forename: Nel
authors.initials: N
authors.lastname: Roeleveld
authors.forename: Lolkje T W
authors.initials: LT
authors.lastname: de Jong-van den Berg
mesh_terms: D000014:Abnormalities, Drug-Induced / Q000517:prevention & control*; D000328:Adult; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects; D011307:Drug Prescriptions / Q000706:statistics & numerical data*; D005260:Female; D006801:Humans; D009426:Netherlands; D010818:Practice Patterns, Physicians' / Q000706:statistics & numerical data*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects; D013723:Teratogens
chemical_list: D016861:Cyclooxygenase Inhibitors; D017367:Selective Serotonin Reuptake Inhibitors; D013723:Teratogens
keywords: congenital abnormalities; pharmaceutical agents; pregnancy; teratology